Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.
Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.
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DOI：
10.1038/srep22522
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发表时间：
2016-03-04
影响因子：
4.6
通讯作者：
Alfano M
中科院分区：
文献类型：
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作者：
Nebuloni M;Albarello L;Andolfo A;Magagnotti C;Genovese L;Locatelli I;Tonon G;Longhi E;Zerbi P;Allevi R;Podestà A;Puricelli L;Milani P;Soldarini A;Salonia A;Alfano M
来自病灶周围和结直肠癌（CRC）而非健康结肠的细胞外基质（ECM）维持肿瘤细胞的增殖和侵袭。我们研究了ECM的生物化学和物理多样性，成对比较健康，病灶周围和CRC标本。从健康到病灶周围和CRC ECM观察到纤维的渐进线性化和组织化程度，并且与刚度和胶原交联的稳定增加相关。在病变周围的ECM这些修改符合血管形成增加，而在肿瘤ECM，它们与改变调制的基质体蛋白，增加含量的羟化赖氨酸和赖氨酰氧化酶。本研究确定了病灶周围ECM的刚度增加和交联，使适合CRC侵袭的环境成为与血管形成相关的现象。结肠区域硬度的增加可能代表促结缔组织增生区域易受侵袭的新的预测标志物，从而为监测具有侵袭潜力的腺瘤提供新的潜在应用。
The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential.